In response to external and internal signals, mammalian cells elicit changes in gene expression patterns that profoundly influence the global cellular response. The transcriptional events that regulate gene expression changes have been thoroughly studied, but less-well understood post-transcriptional processes are emerging as major regulatory mechanisms. Post-transcriptional gene regulation includes pre-mRNA processing and maturation, mRNA transport, stability and translation, as well as protein processing, modification and degradation. We are keenly interested in the mechanisms that regulate the expression of proliferative, cell cycle-regulatory, and stress-response proteins. Over the past 14 years, this Project has examined numerous RBPs, noncoding RNAs, and their influence on gene expression patterns. We have paid particular attention to their influence on the stress and proliferative response of cells, two processes that are severely impaired during aging. In the past funding period, we have studied NF90 and its influence on the stress response(Kuwano et al., Nuc. Acids Res. 2010). Cancer-related studies in collaboration with other laboratories have been focused on HuR in breast cancer (Calaluce et al., BMC Cancer, 2010), HuR in pancreatic cancer (Williams et al., PLoS ONE, 2010), and EBP-1 in prostate cancer (Zhou et al., Nuc. Acids Res. 2010). We have also participated in studies that investigated the influence of RBPs in gastrointestinal homeostasis by focusing on the gut epithelium (Wang et al., Biochem. J., 2010), the impact of polyamines on intestinal integrity (Zou et al., Mol. Cell. Biol., 2010), and liver carcinogenesis (Vazquez-Chantada et al., Gastroenterology, 2010). In a brief meeting report (Black and Gorospe, RNA Biology, 2010), we summarized the state of the field.